2023
The β1-adrenergic receptor links sympathetic nerves to T cell exhaustion
Globig A, Zhao S, Roginsky J, Maltez V, Guiza J, Avina-Ochoa N, Heeg M, Araujo Hoffmann F, Chaudhary O, Wang J, Senturk G, Chen D, O’Connor C, Pfaff S, Germain R, Schalper K, Emu B, Kaech S. The β1-adrenergic receptor links sympathetic nerves to T cell exhaustion. Nature 2023, 622: 383-392. PMID: 37731001, PMCID: PMC10871066, DOI: 10.1038/s41586-023-06568-6.Peer-Reviewed Original ResearchConceptsImmune checkpoint blockadeCell exhaustionExhausted CD8Sympathetic nervesT cell exhaustionSympathetic stress responsePancreatic cancer modelAnti-tumor functionCheckpoint blockadeCatecholamine levelsTissue innervationCytokine productionChronic antigenMalignant diseaseChronic infectionCD8Immune responseAdrenergic signalingEffector functionsΒ-blockersViral infectionCancer modelExhausted stateCell responsesCell functionCirculating and Intratumoral Immune Determinants of Response to Atezolizumab plus Bevacizumab in Patients with Variant Histology or Sarcomatoid Renal Cell Carcinoma
Saliby R, Zarif T, Bakouny Z, Shah V, Xie W, Flippot R, Denize T, Kane M, Madsen K, Ficial M, Hirsch L, Wei X, Steinharter J, Harshman L, Vaishampayan U, Severgnini M, McDermott D, Lee G, Xu W, Van Allen E, McGregor B, Signoretti S, Choueiri T, McKay R, Braun D. Circulating and Intratumoral Immune Determinants of Response to Atezolizumab plus Bevacizumab in Patients with Variant Histology or Sarcomatoid Renal Cell Carcinoma. Cancer Immunology Research 2023, 11: 1114-1124. PMID: 37279009, PMCID: PMC10526700, DOI: 10.1158/2326-6066.cir-22-0996.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaT cellsWorse PFSImmunotherapy responseCell carcinomaPeripheral immune cell populationsWorse progression-free survivalSarcomatoid renal cell carcinomaPhase II clinical trialImmunotherapy-based combinationsValue of tumourPoor-risk patientsProgression-free survivalImmune cell populationsVascular endothelial growth factorKidney cancer diagnosisEndothelial growth factorFuture biomarker studiesLack of responseInflammatory modulesExhausted CD8Variant histologyOverall survivalPD-L1Sarcomatoid differentiationAdrenergic receptors regulate T cell differentiation in viral infection and cancer
Globig A, Zhao S, Roginsky J, Avina-Ochoa N, Heeg M, Chaudhary O, Hoffmann F, Chen D, O’Connor C, Emu B, Kaech S. Adrenergic receptors regulate T cell differentiation in viral infection and cancer. The Journal Of Immunology 2023, 210: 59.13-59.13. DOI: 10.4049/jimmunol.210.supp.59.13.Peer-Reviewed Original ResearchImmune checkpoint blockadeT cell differentiationChronic viral infectionsT cell functionalityT cellsViral infectionAdrenergic receptorsChronic antigen exposureLCMV clone 13Novel immune checkpointT cell proliferationMurine cancer modelsT cell receptor signalingCell differentiationAbstract CD8Terminal-CD8Exhausted CD8Checkpoint blockadeAntigen exposureImmune checkpointsNoradrenaline levelsCell receptor signalingTumor sizeCancer patientsNA receptors
2022
Spatial immune heterogeneity of hypoxia-induced exhausted features in high-grade glioma
Kim A, Choi S, Park J, Kwon M, Chowdhury T, Yu H, Kim S, Kang H, Kim K, Park S, Park C, Shin E. Spatial immune heterogeneity of hypoxia-induced exhausted features in high-grade glioma. OncoImmunology 2022, 11: 2026019. PMID: 35036078, PMCID: PMC8757477, DOI: 10.1080/2162402x.2022.2026019.Peer-Reviewed Original ResearchConceptsHigh-grade gliomasTumor immune microenvironmentTumor-associated macrophagesM2 tumor-associated macrophagesT cellsExhausted CD8Immune cellsImmunosuppressive cellsCTLA-4Hypoxic conditionsImmunosuppressive tumor immune microenvironmentProgression-free survivalRegulatory T cellsSurvival of patientsImmunosuppressive profilePD-1Patient survivalImmune microenvironmentImmune heterogeneityHypoxia signatureCD8Different biological featuresPatientsFlow cytometrySurvival
2021
Progressive immune dysfunction with advancing disease stage in renal cell carcinoma
Braun DA, Street K, Burke KP, Cookmeyer DL, Denize T, Pedersen CB, Gohil SH, Schindler N, Pomerance L, Hirsch L, Bakouny Z, Hou Y, Forman J, Huang T, Li S, Cui A, Keskin DB, Steinharter J, Bouchard G, Sun M, Pimenta EM, Xu W, Mahoney KM, McGregor BA, Hirsch MS, Chang SL, Livak KJ, McDermott DF, Shukla SA, Olsen LR, Signoretti S, Sharpe AH, Irizarry RA, Choueiri TK, Wu CJ. Progressive immune dysfunction with advancing disease stage in renal cell carcinoma. Cancer Cell 2021, 39: 632-648.e8. PMID: 33711273, PMCID: PMC8138872, DOI: 10.1016/j.ccell.2021.02.013.Peer-Reviewed Original ResearchConceptsClear cell renal cell carcinomaM2-like macrophagesRenal cell carcinomaAdvanced diseaseExhausted CD8Cell carcinomaDisease stageAdvanced/metastaticImmune inhibitory pathwaysProgressive immune dysfunctionCell renal cell carcinomaAdjacent non-tumor tissuesTumor immune microenvironmentPro-inflammatory macrophagesM2-like polarizationNon-tumor tissuesMetastatic diseaseImmune dysfunctionWorse prognosisImmune microenvironmentImmune cellsCell dysfunctionExternal cohortInhibitory pathwaysMyeloid compartment
2020
IL-18BP is a secreted immune checkpoint and barrier to IL-18 immunotherapy
Zhou T, Damsky W, Weizman OE, McGeary MK, Hartmann KP, Rosen CE, Fischer S, Jackson R, Flavell RA, Wang J, Sanmamed MF, Bosenberg MW, Ring AM. IL-18BP is a secreted immune checkpoint and barrier to IL-18 immunotherapy. Nature 2020, 583: 609-614. PMID: 32581358, PMCID: PMC7381364, DOI: 10.1038/s41586-020-2422-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesDisease Models, AnimalFemaleHepatocyte Nuclear Factor 1-alphaHistocompatibility Antigens Class IHumansImmunotherapyIntercellular Signaling Peptides and ProteinsInterleukin-18Kaplan-Meier EstimateKiller Cells, NaturalLymphocytes, Tumor-InfiltratingMaleMiceNeoplasmsReceptors, Interleukin-18Stem CellsTumor MicroenvironmentConceptsIL-18IL-18BPT cellsAnti-PD-1 resistant tumorsWild-type IL-18Potent anti-tumor effectsMajor histocompatibility complex class IIL-18 pathwayIL-18 therapyInterleukin-18 pathwayMajor therapeutic barrierStem-like TCF1Anti-tumor immunityTumor-infiltrating lymphocytesNatural killer cellsRecombinant IL-18Histocompatibility complex class IAnti-tumor effectsComplex class IAnti-tumor activityMouse tumor modelsModern immunotherapyPrecursor CD8Effector CD8Exhausted CD8
2019
Author Correction: Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade
Miller BC, Sen DR, Al Abosy R, Bi K, Virkud YV, LaFleur MW, Yates KB, Lako A, Felt K, Naik GS, Manos M, Gjini E, Kuchroo JR, Ishizuka JJ, Collier JL, Griffin GK, Maleri S, Comstock DE, Weiss SA, Brown FD, Panda A, Zimmer MD, Manguso RT, Hodi FS, Rodig SJ, Sharpe AH, Haining WN. Author Correction: Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade. Nature Immunology 2019, 20: 1556-1556. PMID: 31582823, PMCID: PMC7461603, DOI: 10.1038/s41590-019-0528-5.Peer-Reviewed Original ResearchSubsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade
Miller BC, Sen DR, Al Abosy R, Bi K, Virkud YV, LaFleur MW, Yates KB, Lako A, Felt K, Naik GS, Manos M, Gjini E, Kuchroo JR, Ishizuka JJ, Collier JL, Griffin GK, Maleri S, Comstock DE, Weiss SA, Brown FD, Panda A, Zimmer MD, Manguso RT, Hodi FS, Rodig SJ, Sharpe AH, Haining WN. Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade. Nature Immunology 2019, 20: 326-336. PMID: 30778252, PMCID: PMC6673650, DOI: 10.1038/s41590-019-0312-6.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesExhausted tumor-infiltrating lymphocytesT cell dysfunctionExhausted CD8T cellsCheckpoint blockadeCell dysfunctionAnti-PD-1 therapyInhibitory receptor PD-1Chronic viral infectionsExhausted T cellsReceptor PD-1Checkpoint blockade therapyDysfunctional CD8PD-1Antibody blockadeTumor controlSuch therapyCD8Viral infectionTumor growthExhausted cellsSpecific subpopulationsBlockadeTherapy
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